Group B streptococci (GBS) are the major human bacterial pathogens in the neonatal period. Systemic GBS infection during the first two months of life affects approximately three live births per thousand, resulting in 11,000 cases annually in the United States. Substantial numbers of these infants die or have permanent neurologic sequelae from the meningitis associated with this infection. Pregnancy-related morbidity occurs in nearly 50,000 women annually. Immunoprophylaxis has the greatest potential for prevention of both maternal and infant disease due to GBS. Susceptibility to GBS infection has been correlated with low levels of serum antibodies to the sialic acid-containing typespecific capsular polysaccharides. These antibodies cross the placenta and are protective to the neonate. Provision of protective levels of type-specific anti-capsular antibodies to the infant could theoretically be achieved by active immunization of women. The capsular polysaccharides from GBS serotypes Ia, Ib, II, and III have been isolated, purified, immunochemically characterized, and tested as immunogens in healthy adults. Among nonimmune adults, the target population for prevention of GBS-related infection in both adults and infants, immune response following a single 50-ug dose of type Ia, II, or III vaccine is observed in only 40%, 88%, and 57%-73% of subjects. A method of effectively coupling the type-specific polysaccharides to protein carriers to enhance their immunogenicity has been developed. The ability of GBS type-specific polysaccharide-tetanus toxoid (CP-TT) to induce immunity in adults will be the subject of the investigations. Capsular polysaccharides will be conjugated to tetanus toxoid by reductive amination through a selective modification of the terminal sialic acid residues on each repeating unit. Our five Specific Aims are: 1) preparation of CP-TT vaccines against GBS serotypes Ia, lb, II, and III; 2) definition of the antibody response in laboratory animals to GBS CP-TT vaccines; 3) phase I testing of CP-TT vaccines in humans for safety and immunogenicity; 4) determination of optimal dose for CP-TT vaccines; and 5) comparison of tetravalent CP-TT vaccine to tetravalent polysaccharides. Isotype-specific antibody response to the capsular polysaccharides will be measured, and the functional ability of these antibodies to induce protection to GBS will be determined. CP-TT vaccines should induce long-lived IgG antibodies that prevent the devastating effects of GBS in neonates as well as maternal GBS morbidity.